Effect of clenbuterol administration on the healthy murine heart

Abstract

Clenbuterol has recently been shown to reverse pathologic cardiac remodeling during left ventricular assist device (LVAD) support, leading to restored ventricular function and explantation of LVAD devices. However, others have not been able to support these observations. Our hypothesis is that the beta(2)-adrenergic activity of clenbuterol induces cardiac extracellular matrix (ECM) remodeling, resulting in increased interstitial fibrillar collagen content and altered diastolic function that may account for these conflicting reports. The intent of this study is to characterize the effect of clenbuterol on healthy murine hearts with transthoracic echo and histology. C57BL/6 female mice were administered 2.4 microg/kg/day of clenbuterol in the drinking water for 7 days and analysis conducted on day 8-24 hours after the last dose of clenbuterol. Histological analysis demonstrated an increase in left ventricular ECM collagen content in a control group compared with the clenbuterol group (density 0.32 +/- 0.16 compared to 2.01 +/- 0.30 RD/mm(2)). The ventricular fibrosis was supported by altered diastolic function measured by transthoracic echo where there was a significant increase in isovolumic relaxation time, and left atrial dimension and a decrease in left ventricular free wall tissue Doppler ratios. Our study showed no significant differences in left ventricular ejection fraction, cardiac output, or heart rate between the clenbuterol and control groups. These data suggest that the beta-2 adrenergic activity of clenbuterol increases ECM fibrillar collagen concentrations in normal hearts, resulting in altered diastolic function.